title: High incidence of loss of heterozygosity at chromosome 17p13 in breast tumours from BRCA2 mutation carriers.
abstract: Breast tumours from BRCA1 and BRCA2 mutation carriers are genetically instable and display specific patterns of chromosomal aberrations, suggestive of distinct genetic pathways in tumour progression. The frequency of abnormalities affecting chromosome 17p and the TP53 gene was determined in 27 breast tumours from 26 female patients carrying the Icelandic BRCA2 founder mutation (999del5). Loss of heterozygosity (LOH) was detected in 23 of the 27 tumours (85%). The majority of tumours manifesting LOH had lost a large region on 17p, although a more restricted loss, including the TP53 locus was seen in a few tumours. Positive p53 immunostaining was observed in 18 of 26 tumours (69%). However, mutations in the TP53 gene were detected in only three tumours (11%), including a missense (codon 139) and a nonsense mutation (codon 306) in two tumours with moderate p53 expression and a frameshift deletion (codon 182) in a tumour with no detectable p53 expression. Positive p53 immunostaining, mainly weak, was observed in 16 of the 24 tumours (66%) without TP53 mutation. The high frequency of LOH at chromosome 17p13 suggests that one or more genes from this region are involved in the development of BRCA2-induced breast cancer. The frequent finding of weak overexpression of, presumably wild type p53 protein, suggests an alternative mechanism of TP53 involvement specific to these tumours.
authors.affiliation: Department of Pathology, University and National Hospital of Iceland, Reykjavik.
authors.forename: G
authors.initials: G
authors.lastname: Eiriksdottir
authors.forename: R B
authors.initials: RB
authors.lastname: Barkardottir
authors.forename: B A
authors.initials: BA
authors.lastname: Agnarsson
authors.forename: G
authors.initials: G
authors.lastname: Johannesdottir
authors.forename: K
authors.initials: K
authors.lastname: Olafsdottir
authors.forename: V
authors.initials: V
authors.lastname: Egilsson
authors.forename: S
authors.initials: S
authors.lastname: Ingvarsson
mesh_terms: D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D002897:Chromosomes, Human, Pair 7; D004276:DNA, Satellite; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D009363:Neoplasm Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D024682:BRCA2 Protein; D004276:DNA, Satellite; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53